ArticleJCI insight2021
The role of SHP/REV-ERBα/CYP4A axis in the pathogenesis of alcohol-associated liver disease.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 39 citations in OpenAlex.
- Berberine alleviates alcoholic liver diseaseactivating intestinal nuclear receptor subfamily 1 group D member 1.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Timing matters: circadian rhythm disruption in alcohol-associated peripheral organ pathophysiology.Function (Oxford, England) · 2026Review
- Signatures of proteomics and glycoproteomics revealed liraglutide ameliorates MASLD by regulating specific metabolic homeostasis in mice.Journal of pharmaceutical analysis · 2025Article
- Rev‑erbα: The circadian guardian against NLRP3‑driven liver fibrosis.Molecular medicine reports · 2025Article
- Chronic alcohol intake disrupts cytochrome P450 enzyme activity in alcoholic fatty liver disease: insights into metabolic alterations and therapeutic targets.Frontiers in chemistry · 2025Article
- Article
- Human umbilical cord mesenchymal stem cells attenuate diet-induced obesity and NASH-related fibrosis in mice.Heliyon · 2024Article
- Alcohol-associated liver disease.The Journal of clinical investigation · 2024Review
- Targeting NR1D1 in organ injury: challenges and prospects.Military Medical Research · 2023Review
- Single-Cell RNA Transcriptome Profiling of Liver Cells of Short-Term Alcoholic Liver Injury in Mice.International journal of molecular sciences · 2023Article
- Article
- Knockout of secretin ameliorates biliary and liver phenotypes during alcohol-induced hepatotoxicity.Cell & bioscience · 2023Article
- Structural basis of synthetic agonist activation of the nuclear receptor REV-ERB.Nature communications · 2022Article
- Role of Circadian Transcription Factor Rev-Erb in Metabolism and Tissue Fibrosis.International journal of molecular sciences · 2022Review
- Article
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
Alcohol-associated liver disease (ALD) represents a spectrum of histopathological changes, including alcoholic steatosis, steatohepatitis, and cirrhosis. One of the early responses to excessive alcohol consumption is lipid accumulation in the hepatocytes. Lipid ω-hydroxylation of medium- and long-chain fatty acid metabolized by the cytochrome P450 4A (CYP4A) family is an alternative pathway for fatty acid metabolism. The molecular mechanisms of CYP4A in ALD pathogenesis have not been elucidated. In this study, WT and Shp-/- mice were fed with a modified ethanol-binge, National Institute on Alcohol Abuse and Alcoholism model (10 days of ethanol feeding plus single binge). Liver tissues were collected every 6 hours for 24 hours and analyzed using RNA-Seq. The effects of REV-ERBα agonist (SR9009, 100 mg/kg/d) or CYP4A antagonist (HET0016, 5 mg/kg/d) in ethanol-fed mice were also evaluated. We found that hepatic Cyp4a10 and Cyp4a14 expression were significantly upregulated in WT mice, but not in Shp-/- mice, fed with ethanol. ChIP quantitative PCR and promoter assay revealed that REV-ERBα is the transcriptional repressor of Cyp4a10 and Cyp4a14. Rev-Erbα-/- hepatocytes had a marked induction of both Cyp4a genes and lipid accumulation. REV-ERBα agonist SR9009 or CYP4A antagonist HET0016 attenuated Cyp4a induction by ethanol and prevented alcohol-induced steatosis. Here, we have identified a role for the SHP/REV-ERBα/CYP4A axis in the pathogenesis of ALD. Our data also suggest REV-ERBα or CYP4A as the potential therapeutic targets for ALD.
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